New neurons are generated throughout life in distinct regions of the mammalian brain. This process, called adult neurogenesis, has been implicated in physiological brain function, and failing or ...altered neurogenesis has been associated with a number of neuropsychiatric diseases. Here, we provide an overview of the mechanisms governing the neurogenic process in the adult brain and describe how new neurons may contribute to brain function in health and disease.
The mammalian SWI/SNF complex, or BAF complex, has a conserved and direct role in antagonizing Polycomb-mediated repression. Yet, BAF also promotes repression by Polycomb in stem cells and cancer. ...How BAF both antagonizes and promotes Polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-Polycomb axis in mouse embryonic stem cells on short timescales. We report that rapid BAF depletion redistributes Polycomb repressive complexes PRC1 and PRC2 from highly occupied domains, like Hox clusters, to weakly occupied sites normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 and PRC2, we identify a conventional role for BAF in Polycomb-mediated repression, in addition to global Polycomb redistribution. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.
Low levels of oxygen (O2) occur naturally in developing embryos. Cells respond to their hypoxic microenvironment by stimulating several hypoxia-inducible factors (and other molecules that mediate O2 ...homeostasis), which then coordinate the development of the blood, vasculature, placenta, nervous system and other organs. Furthermore, embryonic stem and progenitor cells frequently occupy hypoxic 'niches' and low O2 regulates their differentiation. Recent work has revealed an important link between factors that are involved in regulating stem and progenitor cell behaviour and hypoxia-inducible factors, which provides a molecular framework for the hypoxic control of differentiation and cell fate. These findings have important implications for the development of therapies for tissue regeneration and disease.
We study the mass, velocity dispersion and anisotropy profiles of Λ cold dark matter (ΛCDM) haloes using a suite of N-body simulations of unprecedented numerical resolution. The Aquarius Project ...follows the formation of six different galaxy-sized haloes simulated several times at varying numerical resolution, allowing numerical convergence to be assessed directly. The highest resolution simulation represents a single dark matter halo using 4.4 billion particles, of which 1.1 billion end up within the virial radius. Our analysis confirms a number of results claimed by earlier work, and clarifies a few issues where conflicting claims may be found in the recent literature. The mass profile of ΛCDM haloes deviates slightly but systematically from the form proposed by Navarro, Frenk & White. The spherically averaged density profile becomes progressively shallower inwards and, at the innermost resolved radius, the logarithmic slope is γ≡− d ln ρ/d ln r≲ 1. Asymptotic inner slopes as steep as the recently claimed ρ∝r−1.2 are clearly ruled out. The radial dependence of γ is well approximated by a power law, γ∝rα (the Einasto profile). The shape parameter, α, varies slightly but significantly from halo to halo, implying that the mass profiles of ΛCDM haloes are not strictly universal: different haloes cannot, in general, be rescaled to look identical. Departures from similarity are also seen in velocity dispersion profiles and correlate with those in density profiles so as to preserve a power-law form for the spherically averaged pseudo-phase-space density, ρ/σ3∝r−1.875. The index here is identical to that of Bertschinger's similarity solution for self-similar infall on to a point mass from an otherwise uniform Einstein–de Sitter universe. The origin of this striking behaviour is unclear, but its robustness suggests that it reflects a fundamental structural property of ΛCDM haloes. Our conclusions are reliable down to radii below 0.4 per cent of the virial radius, providing well-defined predictions for halo structure when baryonic effects are neglected, and thus an instructive theoretical template against which the modifications induced by the baryonic components of real galaxies can be judged.
About half of annual marine carbon burial takes place in shallow water ecosystems where geomorphic and ecological stability is driven by interactions between the flow of water, vegetation growth and ...sediment transport. Although the sensitivity of terrestrial and deep marine carbon pools to climate change has been studied for decades, there is little understanding of how coastal carbon accumulation rates will change and potentially feed back on climate. Here we develop a numerical model of salt marsh evolution, informed by recent measurements of productivity and decomposition, and demonstrate that competition between mineral sediment deposition and organic-matter accumulation determines the net impact of climate change on carbon accumulation in intertidal wetlands. We find that the direct impact of warming on soil carbon accumulation rates is more subtle than the impact of warming-driven sea level rise, although the impact of warming increases with increasing rates of sea level rise. Our simulations suggest that the net impact of climate change will be to increase carbon burial rates in the first half of the twenty-first century, but that carbon-climate feedbacks are likely to diminish over time.
Authenticity is a prominent concept in current political discourse. Its popularity in political communication has also inspired a growing but still fragmented body of research in communication ...science. Since this field lacks an integrative conceptualization, this article aims to clarify political authenticity for academic discourse and as a research object for communication science. The article provides a narrative review of research on authenticity in political communication and proposes an understanding of political authenticity as a social construction which is created and negotiated in complex communication processes among politicians, the media, and the audience. I propose performed, mediated, and perceived political authenticity as three analytic perspectives to deconstruct these complex processes and to link political authenticity with media and communication literature. Finally, I derive four dimensions of political authenticity (consistency, intimacy, ordinariness, and immediacy) and corresponding indicators that will help to operationalize it as a strategy by politicians, a product from mediation processes, and as an audience perception.
We present an update to the multiphase smoothed particle hydrodynamics galaxy formation code by Scannapieco et al. We include a more elaborate treatment of the production of metals, cooling rates ...based on individual element abundances and a scheme for the turbulent diffusion of metals. Our supernova feedback model now transfers energy to the interstellar medium (ISM) in kinetic and thermal form, and we include a prescription for the effects of radiation pressure from massive young stars on the ISM. We calibrate our new code on the well-studied Aquarius haloes and then use it to simulate a sample of 16 galaxies with halo masses between 1 × 1011 and 3 × 1012 M. In general, the stellar masses of the sample agree well with the stellar mass to halo mass relation inferred from abundance matching techniques for redshifts z = 0-4. There is however a tendency to overproduce stars at z > 4 and to underproduce them at z < 0.5 in the least massive haloes. Overly high star formation rates (SFRs) at z < 1 for the most massive haloes are likely connected to the lack of active galactic nuclei feedback in our model. The simulated sample also shows reasonable agreement with observed SFRs, sizes, gas fractions and gas-phase metallicities at z = 0-3. Remaining discrepancies can be connected to deviations from predictions for star formation histories from abundance matching. At z = 0, the model galaxies show realistic morphologies, stellar surface density profiles, circular velocity curves and stellar metallicities, but overly flat metallicity gradients. 15 out of 16 of our galaxies contain disc components with kinematic disc fraction ranging between 15 and 65 per cent. The disc fraction depends on the time of the last destructive merger or misaligned infall event. Considering the remaining shortcomings of our simulations we conclude that even higher kinematic disc fractions may be possible for Λ cold dark matter haloes with quiet merger histories, such as the Aquarius haloes.
How carbon (C) flows through plants into soils is poorly understood. Carbon exuded comes from a pool of non-structural carbohydrates (NSC) in roots. Simple models of diffusion across concentration ...gradients indicate that the more C in roots, the more C should be exuded from roots. However, the mechanisms underlying the accumulation and loss of C from roots may differ depending on the stress experienced by plants. Thus, stress type may influence exudation independent of NSC. We tested this hypothesis by examining the relationship between NSC in fine roots and exudation of organic C in aspen (Populus tremuloides Michx.) seedlings after exposure to shade, cold soils and drought in a controlled environment. Fine root concentrations of NSC varied by treatment. Mass-specific C exudation increased with increasing fine root sugar concentration in all treatments, but stress type affected exudation independently of sugar concentration. Seedlings exposed to cold soils exuded the most C on a per mass basis. Through 13C labeling, we also found that stressed seedlings allocated relatively more new C to exudates than roots compared with unstressed seedlings. Stress affects exudation of C via mechanisms other than changes in root carbohydrate availability.
Oxygen (O2) is an essential nutrient that serves as a key substrate in cellular metabolism and bioenergetics. In a variety of physiological and pathological states, organisms encounter insufficient ...O2 availability, or hypoxia. In order to cope with this stress, evolutionarily conserved responses are engaged. In mammals, the primary transcriptional response to hypoxic stress is mediated by the hypoxia-inducible factors (HIFs). While canonically regulated by prolyl hydroxylase domain-containing enzymes (PHDs), the HIFα subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1α (FIH1), sirtuins, and metabolites. These transcription factors function in normal tissue homeostasis and impinge on critical aspects of disease progression and recovery. Insights from basic HIF biology are being translated into pharmaceuticals targeting the HIF pathway.
Nucleosidic and oligonucleotidic diarylethenes (DAEs) are an emerging class of photochromes with high application potential. However, their further development is hampered by the poor understanding ...of how the chemical structure modulates the photochromic properties. Here we synthesized 26 systematically varied deoxyuridine‐ and deoxycytidine‐derived DAEs and analyzed reaction quantum yields, composition of the photostationary states, thermal and photochemical stability, and reversibility. This analysis identified two high‐performance photoswitches with near‐quantitative, fully reversible back‐and‐forth switching and no detectable thermal or photochemical deterioration. When incorporated into an oligonucleotide with the sequence of a promotor, the nucleotides maintained their photochromism and allowed the modulation of the transcription activity of T7 RNA polymerase with an up to 2.4‐fold turn‐off factor, demonstrating the potential for optochemical control of biological processes.
From a library of 26 deoxyuridine‐ and deoxycytidine‐derived diarylethenes we identified two high‐performance photoswitches with near‐quantitative, fully reversible back‐and‐forth switching, high reaction quantum yields and no detectable thermal or photochemical deterioration. Incorporated into an oligonucleotide, these nucleotides allowed the optochemical modulation of the activity of T7 RNA polymerase.
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